Antibiotics have found their way into mainstream human healthcare, veterinary medicine, agriculture, and in many prophylactic uses such as in soaps and sprays since their development in the 1940's. As a result of the ubiquitous use of antibiotics, antibiotic resistant strains of bacteria have evolved that are becoming increasingly difficult to treat. For each bacteria species, sub-species, and even bacterial serotype in existence, a specific bacteriophage exists that infects it. A bacteriophage (phage) is a virus that infects and replicates within a bacterium. The term is derived from “bacteria” and the Greek (phagein), “to devour”. Phages are composed of proteins that encapsulate a DNA or RNA genome, and may have relatively simple or elaborate structures.
Phage applications have recently been approved by the Food and Drug Administration (FDA) to be used in the American food industry to eliminate the presence of specific bacteria such as infectious Listeria, Salmonella, and E. coli from ready-to-eat meats and prepackaged salads as well as to ward off competing bacterial organisms which may arise within the active cultures in various yogurts. Viruses are known to undergo mutation very quickly and even retain mutations which cause them to infect bacteria other than their established host.
Phages have been shown to be effective at neutralizing in vivo bacterial infections as well as an effective prophylactic application to items that may encounter bacterial contamination. Phage, however, are very host specific so searching for, isolating, and propagating phage that are specific to a particular “problem” bacterial strain or serotype can be challenging. That notwithstanding, the current problem with using phage to eliminate (or prevent) infections and/or bacterial contamination is that phage are often too specific to each type of bacterium to be useful against real-world infection or contamination.
This problem has been answered in current industry by creating “phage cocktails” which contain several different variants of phages to combat a single, specific bacterial strain. The Eliava Institute, for example has accumulated an extensive collection of different phages that they use in cocktails to treat bacterial infections in human patients in vivo. Other companies such as Micreos and Intralytix, Inc. have patented phage cocktails targeting Listeria, Salmonella, and E. coli which are currently being sprayed on ready-to-eat foods such as prepackage salads, lunch meats, chicken, and fish. The same phage cocktails are also being used to clean surface contamination in food processing plants as well as on certain crops such as tomatoes and chilies. In addition, using phage applications on crops and livestock falls within the “organic” status for US food production.
What is needed are methods of producing bacteriophages with expanded host-range and bacteriophages with expanded host-ranges that solve the problems and limitations of the prior art.
Wherever possible, the same reference numbers will be used throughout the drawings to represent the same parts.